The present invention relates to magnetic resonance imaging, and more particularly to a method and apparatus for performing functional magnetic resonance imaging (fMRI) in conscious animals.
Human studies utilizing fMRI have advanced our understanding of the regional and functional interplay between populations of neurons serving sensory, integrative and motor functions. Changes in neuronal activity are accompanied by specific changes in hemodynamics such as cerebral blood flow, cerebral blood volume, and blood oxygenation. Functional MRI has been used to detect these changes in response to visual stimulation, somatosensory activation, motor tasks, and emotional and cognitive activity. When the brain is activated by any of these conditions, the blood flow and delivery of oxygen to the active regions the tissue oxygen uptake resulting in an increase in blood oxy-hemoglobin (HbO2) content. The susceptibility difference between diamagnetic oxy-hemoglobin and paramagnetic deoxy-hemoglobin (Hb) creates local magnetic field distortions that affect the processional frequency of the water protons. The consequential change in magnetic resonance (MR) signal intensity which is proportional to the ratio of HbO2 to Hb. These signal-intensity alterations related to blood oxygenation are termed the BOLD (blood oxygenation-level-dependent) effect. The voxels in paramagnetic Hb content is decreased are illuminated in the image.
While most work on fMRI has been done in humans, it has been difficult to use this technology in conscious animals because of motion artifact. As a result, most studies to date have been limited to animals which are typically anesthetized in order to minimize this problem of motion artifacts. The low level of arousal during anesthesia either partially or completely suppresses the fMRI response and has impeded fMRI application to the more physiologically relevant functions that have been noted in humans.
Since image resolution is a salient feature of fMRI, precautions to ensure improved image quality with minimized head movements are essential. In addition to head movement, it has been observed that any motion outside the field of view can obscure or mimic changes in signal.
Another, equally significant component for achieving high temporal and spatial image resolution is the generation of radiofrequency (RF) magnetic fields. The RF field pulses are transmitted to flip protons into the transverse plane of the main direct current (DC) magnetic field. As these protons precess and relax back into the longitudinal plane of the main magnetic field they emit RF magnetic field signals. The electrical assemblies capable of sending and receiving RF signals are called RF probes, coils, or resonators. Ideally, a RF coil used for magnetic field transmission creates a large homogenous area of proton activation at a very narrow bandwidth center around the proton resonance frequency with minimal power requirements. An RF coil used for receiving covers the largest region of interest within the sample at the highest signal-to-noise ratio (SNR). RF coils are either volume coils or surface coils. A volume coil has the advantage of both sending and receiving RF signals from large areas of the sample. However, signal-to-noise ratio is compromised because a large spatial domain contributes to the RF signal, resulting in additional noise and thereby obscuring the RF signal from the region of interest. A surface coil has the advantage of improved SNR due to its close proximity to the sample. Unfortunately, a surface coil is ill suited for RF energy transmission owing to the fact that only a small proton area can be activated. Two criteria are sought in the design of superior coil performance for high field animal studies. First, the coils must be as efficient as possible. Transmission efficiency is increased by reducing the resistive coil losses through appropriate arrangement of conductors, the use of a shield, and the employment of low loss dialectric materials. By using a separate surface coil in proximity over the desired field of view (FOV) or region of interest, the reception efficiency of the acquired NMR signal is further increased. In imaging, spatial and temporal resolutions are proportional to SNR.
The second criterion to be met for a volume coil, is the uniformity or homogeneity over a desired FOV in the animal sample. To achieve both homogeneity and efficiency for volume coils of Larmor wavelength dimensions, further improvements are required. Conventional state-of-the-art birdcage coil designs will not resonate at these dimensions.
So-called transversal electromagnetic (TEM) resonator designs have shown promise for high-frequency, large volume coil applications for humans. However, these TEM designs must be improved upon for the highest frequency and animal applications allowed by present and future magnets, e.g; for the 9.4T, and the 11.74T, magnets presently being built for laboratory animal studies.
Increased SNR is sought by making NMR measurements at higher magnetic, or Bo, fields. Main magnetic field strength is, however, only one of several parameters affecting the MR sensitivity. RF coil and tissue losses can significantly limit the potential SNR gains realized at high fields. SNR (and reciprocal transmission efficiency) will suffer when the coil""s ohmic resistance, radiation resistance, coupled issue losses, RF magnetic field and angular frequency are not optimized.
Tissue losses increasingly impact SNR at higher frequencies. These conductive and dielectric losses represented are limited in practice by using local surface coils, or volume coils efficiently coupled to a region of interest. In addition to tissue loading, RF losses in the coils themselves become significant at higher frequencies. The RF coil loss increases with frequency as do the resistive losses in the coil RC, which increases with the square root of the angular frequency, and the losses from radiation resistance, which increases as at the fourth power of the angular frequency. The radiation losses also increase as the coil size increases as S2, where S is the area bounded by the coil.
From the above, it is apparent that radiative losses to the sample and environment, as well as conductive losses to the load of a coil become severe to the point of limiting and eventually degrading the SNR gains otherwise expected at higher magnetic field strengths. Physically, as a coil is increased in dimension and/or frequency, its electrical circuit length increases, the coil ceases to behave like a xe2x80x9ccoilxe2x80x9d (RF field storage circuit) and begins to behave more like an xe2x80x9cantennaxe2x80x9d (RF field energy radiator).
Applicant""s method and apparatus overcomes the difficulties of performing fMRI on conscious animals by utilizing a restraining assembly to eliminate movement artifacts in combination with RF resonator system to enhance MR signal for mapping changes in brain activity. The restraining assembly incorporates a coil design including a spatially adjustable volume coil for transmitting RF magnetic field pulses and a spatially adjustable dome shaped surface coil for receiving the RF response signals from the conscious animal. The significance of applicant""s method of neuroimaging in conscious animals will change current imagery of the brain from either a static (as seen with most neurochemical measurements) or a low activation dynamic system in an anesthetized state (as seen with current fMRI or positron emission tomography (PET) measurements) to more physiologically relevant conditions.
There are two approaches to remedy the problem of high-frequency radiative losses: 1) construct smaller coils or array elements; and 2) build coils by transmission line or transverse electromagnetic (TEM) principles. Transmission lines eliminate radiative loss. Often it is desirable to transmit with a larger homogeneous TEM volume coil and receive with a smaller, closer fitting surface coil. However, to operate a transmitting TEM volume coil in conjunction with a receiving surface coil, or an array surface coil, involves switching circuits and an active tuning/detuning methodology. Thus, the present invention employs a coil mounted on a restraining assembly.
A preferred embodiment of the present invention immobilizes the head and body of conscious animals for several hours, without compromising physiological functions. The apparatus allows for collection of a consistent voxel by voxel representation of the brain over several data acquisitions under various experimental conditions. Applicants have demonstrated fMRI signal changes with high temporal and spatial resolution in discrete brain areas in response to electrical stimulation, such as footshock and during odor stimulation. Changes are measured in conscious animals with and without the use of contrast agents. Importantly, the information is obtained without injury to the animal and provides a method of performing developmental measurements on the subject over the course of its life.
The single or multi-cylindrical non-magnetic restraining assembly immobilizes the head and body of conscious animals for insertion into the bore of a magnetic resonance (MR) spectrometer.
A restraining assembly according to the invention for imaging conscious animals includes a head restrainer that restrains the head of the conscious animal, a body restrainer that restrains the body of the animal, and a frame on which the volume coil is mounted. The frame carries both the head restrainer and the body restrainer and has a damping structure for reducing transmission of movement from the body restrainer to the head restrainer.
In an embodiment of the invention, the multi-cylindrical non-magnetic dual-coil animal restrainer to immobilize the head and body of a conscious animal has a cylindrical body restrainer, and a cylindrical head restrainer that are concentrically mounted within the frame.
The frame can also include an adapter to slide into the bore of the MR spectrometer and adjust the diameter of the frame to the inner diameter of the bore. The frame unit includes a first front-end mounting plate having an access hole extending through the plate, a second or rear-end mounting plate parallel and spaced from the front-end mounting plate and having an access hole extending through the second plate, and a plurality of support members or rods extending between the mounting plates to space and support the mounting plates in relative position, wherein the support rods reduce transmission of movement of the body restrainer to the head restrainer, thereby decoupling vibration between the mounting plates. The support rods also act as rails for sliding and positioning the cylindrical volume coil over the head and body restrainers.
The body restrainer holds the body of the conscious animal. The body restrainer can include an elongated cylindrical body tube carried by the frame and a shoulder restrainer carried by the cylindrical body tube that positions of the animal""s shoulders once the head restrainer is secured into the front-end mounting plate. The front of the body tube fits into a ring on the backside of the front-end mounting plate. The seal between the front of the body tube and the ring on the front-end mounting plate is cushioned by a rubber gasket to decouple vibration between the body restrainer and the head restrainer.
The head restrainer immobilizes the head of the conscious animal. The head restrainer includes a cylindrical head holder having a bore to receive and restrain the head of an animal, and a docking post at the front of the head restrainer for securing the head holder to the front-end mounting plate.
The head holder restrains the head of the animal to prohibit vertical and horizontal movement of the animal during imaging. The head holder has a bite bar extending horizontally creating a chord along the bottom of its circular aperture. A vertical nose clamp extends through the top of the head holder and abuts the animal""s nose to clamp the animal""s mouth thereon.
The animal""s head is further restrained by a pair of lateral ear clamping elements or screws that extend horizontally through bilateral openings or the sides of the head holder and a nose clamp that extends vertically through the head holder. A protective ear piece is placed over the animal""s ears and receives the tips of the lateral ear clamping screws.
A further adaptation of an embodiment includes a restraining jacket to restraining an animal and prohibit limb movement. An animal is placed into the restraining jacket. Holders for the arms and legs may be used to further restrict the animal""s movement.